Abstract MS- 2 tumor produced in BALB/c mice by transplant of in vitro cultivated cells derived from a primary MSV-M tumor in mice did not show spontaneous regression but grew progressively and killed the host. The MS- 2 tumor was histologically classified as a malignant sarcoma. In syngeneic BALB/c mice, the i.m. transplanted MS- 2 tumor had a mean doubling time of 2.5 days when the tumor mass was 500 mg and 14 days when the tumor reached 4.0 g. MS- 2 tumor cells showed a high ability to metastatize (tested by bioassay). The organ mainly involved was the lung. In a small percentage of mice, metastases were also detected in spleen, liver, kidney, brain and blood. The activity of: cyclophosphamide, daunorubicin, adriamycin and 4′-epi-adriamycin on the MS- 2 tumor was evaluated. The effects on both tumor growth and pulmonary metastases were detected. In parallel, the drugs were tested on the highly immunogenic T-MSV tumor, obtained by serial. in vivo passages of the primary MSV-induced tumor. Daunorubicin did not have any therapeutic effect on the growth of MS- 2 tumor; adriamycin produced a marked delay of the tumor growth and a significant increase of the life span; cyclophosphamide produced a longer delay in tumor growth than adriamycin did, but the life span was only slightly increased. On the T-MSV tumor, daunorubicin and adriamycin reduced tumor growth and did not affect spontaneous tumor regression; cyclophosphamide reduced tumor growth but completely abolished the spontaneous regression. Adriamycin and its new derivative 4′-epi-adriamycin, given to mice in which the MS- 2 tumor had been surgically removed, inhibited the presence of tumor cells at the lung level. The MS- 2 tumor studied in parallel with the T-MSV tumor allows the comparison of drug activity on a highly or weakly immunogenic tumor. Moreover, the MS- 2 tumor is a viable model for studying the activity of chemotherapeutic drugs on lung metastases and their adjuvant effect on surgery.